Actarit

Site-selective modification of complex functional molecules that contained diverse functionality held great challenges and synthetic promise. Herein, we developed amide-facilitated distal C-H alkynylation and dehydrogenation and multiple C-H alkynylation, switched by Ir(III) catalysis with a Ag(I) or Cu(II) oxidant. Switchable remote and dehydrogenative C-H alkynylation of drug actarit was achieved. Significantly, by exploration of directing priority and judicious amide directing groups, late-stage modification of celecoxib that bears strongly coordinating heterocycles with tunable site selectivity was also realized.

A nonconventional oxidative denitrogenative radical transacetylation method for the chemoselective N-acetylation of primary and secondary aryl/heteroaryl amines using acetohydrazide as a new source of acetyl radical has been discussed. This method, conducted under mild, transition-metal-free conditions in water, offers significant advantages over existing acetylation strategies, which largely rely on harsh reagents such as acetic anhydride, acetyl chloride, or enzyme catalysts. The process utilizes environmentally friendly reagents, namely, tert-butyl hydroperoxide (TBHP) and tert-butyl ammonium iodide (TBAI), to generate acetyl radicals through the oxidative cleavage of acetohydrazide, enabling efficient and selective N-acetylation of a wide variety of amines, including those bearing other sensitive functional groups. Control experiments with radical scavengers confirmed the in situ generation of the acetyl radical, providing strong evidence for the proposed mechanism. Importantly, this protocol demonstrates excellent scalability with successful application in the synthesis and late-stage functionalization of pharmaceutical compounds and advanced drug intermediates. The method not only expands the toolkit for amine functionalization but also offers a sustainable and scalable approach for industrial applications in drug discovery and development.